1. Field of the Invention
This invention relates to a method for the production of an .alpha.-aryl-alkanoic acid. More specifically, this invention relates to a method for the production of an .alpha.-aryl-alkanoic acid represented by the general formula II: Ar--CH(R.sup.3)COOH.
2. Description of Prior Art Many of the compounds represented by the aforementioned general formula II show pharmacological actions. For example, .alpha.-(p-isobutylphenyl)-propionic acid, the species having a p-isobutyl phenyl group as Ar and a methyl group as R.sup.3, is Ibuprofen, a compound useful as antiphlogistics, analgesic, and antipyretics. Numerous attempts have been made to date to obtain .alpha.-aryl-ethanoic acid represented by the general formula IV, Ar--CH(CH.sub.3)--COOH, from an arylethyl ketone represented by the general formula III, Ar--CO--CH.sub.2 CH.sub.3. Typical examples are as follows.
U.S. Pat. Nos. 4,142,054, 4,107,439 and G.B. Pat. No. 1,535,690A: ##STR3## To be used cyclically as Tl (III).
This method uses an expensive and highly toxic thallium (III) salt and, therefore, requires meticulous care to be directed to preventing thallium from mingling into the product intended as a medicine, rendering it inevitable to increase the number of steps involved in the production. The method further uses an expensive raw material, i.e. acetiminoether hydrochloride, and proves disadvantageous from the economic point of view.
(2) K. Fujii et al: Synthesis, 444 (1983): ##STR4##
This method also uses the highly toxic thallium (III) salt and, therefore, requires meticulous care to be directed to preventing thallium from mingling into the product intended as a medicine. It further uses an expensive trialkyl ester of ortho-formic acid and proves expensive.
(3) Andre Goosen et al: J. chem. Soc., Commun., 1311-1312 (1982): ##STR5##
This method turns out to be an expensive approach because it is required to use as much as 4 mols of expensive ICl on an alkyl-aryl dioxolane which is obtained as an intermediate.
(4) E.P. Pat. No. 48,136A: ##STR6##
This method is uneconomical and expensive because it involved a complicated and highly roundabout procedure consisting of many steps.
(5) E.P. Pat. No. 34,871A and U.S. Pat. No. 4,414,405: ##STR7##
Although this method uses a halogenide or a sulfate of metal as the Lewis acid, it is required to carry out the reaction mainly in a nonpolar medium under an anhydrous condition. Among the catalysts effective at all in the reaction, those which are particularly effective turn out to be harmful metal salts. Since the reactants are highly corrosive, this method entails an expensive operation. This method also has the disadvantage that the refinement of the product requires meticulous care.
(6) E.P. Pat. No. 101,124A: ##STR8##
This method carries out the reaction mainly in the presence of a weakly basic compound such as an organic amine or an alkali or alkaline earth metal salt and, consequently, limits the medium for the reaction to a polar protonic solvent such as an aqueous alcohol or glycol. The catalyst is required to be used at least in an equimolar amount relative to the acetal. The method, as evaluated by repeating the procedures of working examples cited in the specification, is found to have the disadvantage that the reaction velocity is low and the yield is also low.
An object of this invention, therefore, is to provide a novel method for the production of an .alpha.-aryl-alkanoic acid.
Another object of this invention is to provide a method for producing an .alpha.-aryl-alkanoic acid in a high yield by using a safe and inexpensive catalyst instead of either using any of the expensive catalysts and raw materials necessary for the conventional methods or using a toxic catalyst or a chemical liable to explode.
Yet another object of this invention is to provide a method for the production of an .alpha.-aryl-alkanoic acid by a very simple procedure.